This is a K-award resubmission (Mentored Research Scientist Development Award, KOl) that is designed to enable the applicant to acquire a richer clinical understanding of the complex interplay between psychiatric and medical illness, to integrate clinical knowledge with quantitative expertise, and to develop neuroimaging methods that are more clinically useful. The candidate is an Assistant Professor of Radiology and physicist in the positron emission tomography (PET) facility at the University of Pittsburgh. The applicant's primary research experience has been in kinetic modeling and methods development for PET imaging and this quantitative expertise has acted as a bridge between different clinical disciplines. Past and present collaborations include PET studies of medically healthy depressed subjects and skeletal muscle function in subjects with diabetes. These experiences led the candidate to become interested in the link between depression and diabetes. The KOl research will use PET imaging to study diabetes as a co-existing medical illness in elderly depressives. PET measures of serotonin 5-HT1A receptor binding ({11C]WAY 100635) wifi be obtained in subjects with adult-onset type 2 diabetes, 40-80 years of age, who are (n=25) and are not (n=25) depressed. Data interpretation will be facilitated by cerebral blood flow (~l50]water) data that also will be acquired for each subject and by the availability of 5-HT1A and cerebral blood flow measures in medically healthy mid-life and elderly subjects, without and with depression (through ongoing University of Pittsburgh collaborations).